An 8-month-old girl with a history of asphyxia and respiratory distress immediately after birth was hospitalized at her fourth month of age with the diagnosis of kidney infection and it was revealed that she had a unilateral multicystic dysplastic kidney. In recent admission, she presented to emergency room with fever, hyperpnea, and apnea. In appearance, she was a hypotonic girl with broad forehead, hypertelorism, depressed nasal bridge and bitemporal regions, rapid vertical and horizontal nystagmus, and open mouth with salivation. In spite of normal physical growth, she had delayed developmental milestones. Blood gas O 2 saturation dropped after she received phenobarbital. Her urinary and blood tests were normal; however, her cranial magnetic resonance imaging (MRI) revealed vermis agenesis and molar tooth sign. These physical and para-clinical findings suggested Joubert syndrome.

Joubert syndrome is an autosomal recessive disorder named after the French neurologist who introduced it first in 1969, [1] with manifes­tations that included hyperpnea, eye movement disorder, mental retardation, and ataxia and vermis agenesis. [2] It was as a familial disorder in four cases and sporadic in one case. Another classification was given based on the presence of retinal degeneration and renal cystic disease, which worsens the prognosis. Retinal dysplasia has a strong association with cystic renal disease and is an ominous sign for survival. In patients with retinal ano­malies, it is advised to monitor the renal func­tion and perform ultrasonography of kidneys to detect the cystic renal disease. Location of the affected gene of this disorder has not been identified definitely, so clinical and radiolo­gical signs are necessary for the diagnosis of Joubert syndrome. [3] Another aspect of this dis­order is the extreme sensitivity of the patients to the effects of respiratory depressants such as anesthetic agents, opioids, and nitrous oxide. Therefore, these agents should be avoided and close preoperative respiratory monitoring is essential. [4]

Case Report

An 8-month-old girl, who was born as a full-term baby to non-relative parents, was deli­vered by cesarean section with a low Apgar score. The baby presented with respiratory distress and was admitted to neonatal intensive care unit (NICU) for tachypnea and hypotonia. After seven days, she was discharged from the hospital, but her mother noted continued hypo-tonia and abnormal eye movements of her baby. She had no ptosis or abnormal move­ments such as twitching or seizure. Her limb appearance was normal; no polydactyly or de­formity could be seen. Her family history was unremarkable for a similar condition. She was investigated for mental retardation and hypo-tonia, and supportive therapy was recommen­ded. All routine laboratory and special meta­bolic tests including blood and urine amino acid level, serum lactate, and ammonia were within normal limits. Eye examination was performed during the 4 th month of life and the ophthalmologist suspected the presence of Leber amaurosis.

During an episode of high fever, which de­noted urinary tract infection, unilateral atrophic dysplastic kidney was diagnosed along with compensated hypertrophy of the contra-lateral side. In her voiding cystoureterography, there was no reflux except some residue after voiding, and dimercaptosuccinic acid (DMSA) scan detected one functioning kidney without a scar [Figure 1].

Figure 1: Renal Tc-99DMSA: Activity seen only in left kidney along with compensated hypertrophy and normal creatinine indicated that we are not opposed to dysplasia in this kidney.

In her last presentation to the emergency de­partment, the patient was admitted because of high fever, illness, hyperpnea, and complaint of dysuria. During the X-ray imaging, she had respiratory difficulty and because of nystag­mus and some suspected seizure-like move­ments, phenobarbital was prescribed and she was transferred to intensive care unit. Her CXR and sepsis work-up revealed no serious infection, but her ventilation became worse and her hypotonia and mental status deterio­rated during serial observations. After two days, phenobarbital was replaced with pheny-toin. Later, her general condition improved and oxygen requirement decreased, and a feeding tube was inserted and nutrients with supple­ments including B group vitamins (B1, biotin, riboflavin, B12), vitamins C, E, and carnitine solution were started. Her brain magnetic resonance imaging (MRI) revealed vermis age­nesis and a molar tooth sign [Figure 2]a-d.

The patient was diagnosed as Joubert syn­drome. Her parents were advised to continue rehabilitation therapy and to maintain anti-gastroesophageal reflux position for her, and vitamins and carnitine were prescribed. She was discharged after seven days. Before dis­charge, her physical growth indexes were nor­mal: weight 8,250 g, height 74 cm (both above 50% standard growth curve), and head circum­ference 46 cm (upper limit of normal for age and sex). Her development was obviously re­tarded with speech as unrecognizable high pitch sounds. She could show affection and recognize her parents, but could not hold her neck, and profuse salivation was prominent. Other remarkable physical examinations were rapid horizontal and vertical nystagmus, hyper-telorism, prominent forehead, bitemporal de-presssion, depressed nasal bridge, and open mouth [Figure 3].

Figure 3: Bitemporal and nasal bridge depression, open mouth, large head (prominent forehead), and nystagmus are characteristics of Joubert syndrome.

In 1997, association of Joubert syndrome with renal cystic disease and liver fibrosis was reported. [5] In our case, unilateral degenerated multicystic dysplastic renal disease and Leber amauresis and abnormal eye movement were noticeable; however, there was no associated ptosis, polydactyly, or liver fibrosis. In a study of lactate and pyruvate levels in muscle biopsies including the relation of mitochondrial disorders and some forms of this syndrome was described. [6] In our case, serum levels of lactate and pyruvate were nor­mal, but the response to carnitine and vitamin B group was prominent. In 1993, this syndrome was divided into two groups: with and without retinal dystrophy. The retinal dystrophy group presented as a familial form and was associated with renal cystic disease. [7],[8] However, our patient's condition was a sporadic case.

Fifteen years follow-up of 29 patients re­vealed normal laboratory findings; however, 12 of 29 patients were able to walk and 5 of 29 could reach school; behavioral disorder was prominent in this syndrome. [9] In our case, phy­sical growth was normal, the patient was able to recognize only parents and sit with support and hold neck for 10 seconds, and her speech was limited to unclear sounds. Phenotype of this syndrome was defined in some reports [10],[11] and characterized by low-set ears, prominent forehead, wide open mouth, protrusion of tongue due to soft tissue swelling in the base of the mouth, and polydactyly. In our case, there was low-set ears, prominent forehead, wide open mouth and hypertelorism, and large head circumference (98 th percentile for age and gender), although other signs like large tongue and polydactyly were absent.

Dekaban-Arima and Senior-Loken syndrome are disorders that have retinal and renal in­volvement along with molar tooth sign in brain scan, but these disorders have progressive renal failure and polyuria and polydipsia, [12] which were not present in our case. An important concern about Joubert syn­drome patients is their sensitivity to respira­tory suppressive drugs, especially during anes­thesia induction for surgery operation [4] as in our case at birth time and following use of Phenobarbital.

Ultimately, some questions remain about this disorder such as effectiveness of carnitine and vitamin B group in treatment. Association of vesico-ureteral reflux and bladder dysfunction as a part of renal and neurological compli­cations in Joubert syndrome needs prolonged follow-up in a large population.

Acknowledgment

The authors would like to thank H. R. Malaki for his financial support.